Departamento de Farmacia y Tecnologia Farmaceutica, Facultad de Farmacia, Universidad de Sevilla, Sevilla, Spain.
Departamento de Bioquimica y Biologia Molecular, Facultad de Farmacia, Universidad de Sevilla, and Instituto de Biomedicina de Sevilla (IBiS), Hospital Universitario Virgen del Rocío/CSIC/Universidad de Sevilla, Sevilla, Spain.
Curr Pharm Des. 2018;24(14):1589-1616. doi: 10.2174/1381612824666180403113015.
Neurodegenerative diseases, like Alzheimer´s and Parkinson´s disease, are a group of disorders that have in common their increasingly high prevalence along with the shortage of effective treatments. In addition, the scientific community faces the challenge of getting the drugs used in these treatments to cross the blood-brain barrier (BBB) and reach the brain in sufficient concentration to be able to exert its effect. Hence, researchers across multiple disciplines are working together in order to improve the ability of therapeutics to penetrate the BBB. In this sense, the use of nanomedicine, nanoscale structures for drug delivery, exhibits a really high therapeutic potential in the field of neurodegenerative diseases therapy. Since there is new evidence that neuroinflammation produced by reactive microglia contributes to the activation and pathogenesis of neurological disorders, many investigations focus on the identification of new targets whose inhibition can reduce, totally or partially, microglial activation. This review analyzes a wide variety of compounds as possible candidates to achieve this target, from compounds with a natural origin to anti-diabetics, antidepressants, antibiotics and hormones. We also discuss the different strategies to enhance the capacity of these compounds to cross the BBB. Although this review focuses on PLGA nanoparticles as one of the most versatile drug delivery nanosystems, we also describe other strategies, such as direct intranasal administration (nose-tobrain), novel viral vectors and novel implanted catheters.
神经退行性疾病，如阿尔茨海默病和帕金森病，是一组疾病，它们共同的特点是患病率越来越高，而有效的治疗方法却很缺乏。此外，科学界面临的挑战是让这些治疗中使用的药物穿过血脑屏障（BBB），并以足够的浓度到达大脑，以发挥其作用。因此，多个学科的研究人员正在合作，以提高治疗药物穿透 BBB 的能力。在这方面，纳米医学，即用于药物输送的纳米级结构，在神经退行性疾病治疗领域表现出了非常高的治疗潜力。由于有新的证据表明，由反应性小胶质细胞产生的神经炎症有助于神经紊乱的激活和发病机制，因此许多研究都集中在确定新的靶点上，这些靶点的抑制可以完全或部分减少小胶质细胞的激活。这篇综述分析了各种各样的化合物作为可能的候选物来实现这一目标，从具有天然来源的化合物到抗糖尿病药物、抗抑郁药、抗生素和激素。我们还讨论了增强这些化合物穿透 BBB 能力的不同策略。虽然这篇综述侧重于 PLGA 纳米颗粒作为最通用的药物输送纳米系统之一，但我们也描述了其他策略，如直接鼻内给药（鼻内给药）、新型病毒载体和新型植入导管。
